Peginterferon α-2b Injection for Hydroxyurea Resistant or Intolerant ET

Inclusion Criteria:

• Male or female subjects, aged greater or equal to 18 years old at screening;

• Subjects diagnosed as high-risk ET according to the World Health Organization (WHO) 2016 criteria：1) who is older than 60 years and JAK2V617F positive at screening, 2)or who previously suffered from disease-related thrombosis or hemorrhage;

• Subjects who have previously received HU for ET, and the time interval between thelast HU dose and the first dose of the study drug should not be less than 7 days;

• Interferon treatment-naïve, and for those who have previously received interferonthe the time interval between the last dose of interferon and randomization shouldnot be less than 1 month;

• Patients with confirmed hydroxyurea resistance or intolerant, as at least one of thefollowing criteria is met:

1. Platelet count remain greater than 600×10^9 /L after at least 3 months of HUtreatment at a dose ≥2g/d (dose ≥2.5 g/d if subject weight > 80 kg);

2. Platelet count greater than 40010^9/L while white blood cell (WBC) count lowerthan 2.510^9/L, or platelet count greater than 400*10^9 /L while hemoglobinlower than 100 g/L at any dose of HU;

3. Presence of HU-related toxicities at any dose of HU: e.g. ulcers in legs, orany unacceptable skin mucosal manifestations or fever;

• Platelet counts > 450*10^9/L at screening;

• Neutrophil count ≥1.0*10^9/L at screening;

• Haemoglobin ≥11 g/dL at screening for males and 10 g/dL for females at screening;

• There is no serious function damage in liver and kidney: total bilirubin ≤1.5 upperlimit of normal (ULN), alanine aminotransferase≤2.0 ULN, aspartateaminotransferase≤2.0 ULN, prothrombin time is prolonged by less than 4 seconds,Creatinine clearance ≥50 mL/min (according to Cockcroft-Gault formula) at screening;

• Both male and female subjects must agree take an appropriate contraceptive method,including:

1. Male subjects: must agree to use reliable contraception from inform consentuntil 6 months following the last dose of the study drug.

2. Female subjects: Must meet at least one of the following conditions: i) Women without childbearing potential; ii) Women of childbearing potential: nopregnant or breastfeed, negative in blood pregnancy test within 4 days prior to thefirst dosing, and must agree to use reliable contraception from inform consent until 6 months following the last dose of the study drug;

• Subjects understand the objective, characteristic, method and possible adversereactions of the study, voluntarily participate in this study, and sign informedconsent.

Exclusion Criteria:

• History of any other myeloproliferative tumors, or evidence of the presence of anyother myeloproliferative tumors;

• Contraindications or hypersensitivities to interferons of any of its excipients;

• Severe medical conditions or serious comorbidities that the investigators determinedcould jeopardize the safety or protocol adherence, e.g. New York Heart Association [NYHA] Class III-IV, congestive heart failure, symptomatic arrhythmias，pulmonaryhypertension;

• History of major organ transplantation;

• Documented autoimmune disease or history of autoimmune disease at screening, e.g.medication un-controlled thyroid dysfunction, autoimmune hepatitis, idiopathicthrombocytopenic purpura, scleroderma, psoriasis, or any autoimmune arthritis;

• Clinically significant pulmonary infiltration, infectious pneumonia, andnon-infectious pneumonia at screening that, in the investigator's opinion, wouldjeopardize the safety of the subject or their compliance with the protocol;

• Infection with systemic clinical manifestations at screening, e.g., bacteria, fungi,human immunodeficiency virus, excluding hepatitis B and/or C;

• Evidence of severe retinopathy, e.g., cytomegalovirus retinitis, symptomatic maculardegeneration, or clinically significant eye disease, e.g. due to diabetes mellitusor hypertension;

• Diagnosed clinically significant depression or a history of depression and, in theinvestigator's opinion, previous suicide attempts or at any risk of suicide atscreening;

• Diagnosed clinically significant neurological disease or a history of clinicallysignificant neurological disease, except for a history of stable cerebral thrombosisor cerebral hemorrhage;

• History of any malignancy within 5 years (except stage 0 chronic lymphocyticleukemia, basal cell carcinoma, squamous cell carcinoma, and superficial melanoma);

• A history of alcohol or drug abuse within 1 year;

• Have used any investigational drug within 4 weeks prior to first dose ofinvestigational drug, or not recovered from the effects of prior investigationaldrug administration;

• Other situations that, in the investigator's opinion, not appropriate for inclusion.